Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Histamine was coupled to poly(L-glutamate) (PLG) to give a copolymer, poly(glutamylhistamineglutamate) (PHG), with approx. 40% of carboxyl groups in PLG being modified. Unlike either poly(L-histidine) (PLH) or PLG, PHG precipitated only in buffers with pH between 4 and 5. A complex was formed between PHG and poly(L-lysine) (PLL) at pH 7, but it was rapidly dissociated at pH 5 or lower. When PHG-linked transferrin (Tf-PHG) was used to deliver a PLL-conjugated [3H]methotrexate ([3H]MTX-PLL) in K562 leukemia cell cultures, an intracellular accumulation of the radioactivity was observed. These results suggest that a copolymer with both imidazole and carboxyl groups can be useful in the design of acid-sensitive, carrier-mediated drug delivery systems.
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PMID:Acid-sensitive dissociation between poly(lysine) and histamine-modified poly(glutamate) as a model for drug-releasing from carriers in endosomes. 169 60

Two species of DHFR were identified in wild-type L1210 murine leukemia cells by analysis of the kinetics of the binding of MTX and dissociation of the MTX-enzyme complex at pH 5.0 and pH 7.2. The two forms of DHFR were also distinguished by immunoinhibition of the binding of MTX and the catalytic reduction of FH2 to FH4 using an antiserum raised to the purified high affinity form of DHFR. The Ka for the binding of MTX by the low affinity form of the enzyme is 4.5 x 10(7) M-1, substantially lower than the reported Ka for the binding of this drug by the high affinity enzyme. The low affinity form of the enzyme catalyzed the reduction of FH2 to FH4 at a rate slower than the high affinity form of DHFR.
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PMID:Evidence for kinetic and immunologic heterogeneity of dihydrofolate reductase in L1210 leukemia cells. 178 10

The present study provides evidence that green tea extract (GTE), consisting of polyphenol components, is a highly active nucleoside transport inhibitor. GTE markedly inhibited radiolabeled thymidine and uridine transport in mouse leukemia L1210 cells, with IC50 values of 3.2 and 8.0 mumol/L, respectively. GTE blocked the rescue effect of exogenous nucleosides and enhanced the cytotoxicity of AraC and MTX to L1210 cells and human hepatoma BEL-7402 cells. GTE markedly potentiated the inhibitory effect of AraC on leukemia L1210 and P388 in mice. These results indicate that GTE is potentially useful when combined with antimetabolites in cancer chemotherapy.
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PMID:Green tea extract inhibits nucleoside transport and potentiates the antitumor effect of antimetabolites. 178 98

Title compounds were synthesized by condensation of 5-chloro-2,4,6-triaminoquinazoline (8) with various substituted benzaldehydes to produce the corresponding Schiff bases, followed by reduction with NaBH4, II and III were obtained by formylation or nitrosation of I respectively. Primary screening for suppressive therapeutic effects against P. berghei in mice showed that eight of the twelve compounds produced 100% suppression when administered orally at dose of 20 mg/kg. The results against L1210 Leukemia cell and B16 melanoma cell in vitro exhibited potent inhibition. Among them four compounds were more active than MTX and SIPI 759. Further work is in process. Antibacterial tests in vitro showed that a number of compounds possessed moderate activities against Diplococcus pneumoniae.
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PMID:[Synthesis and biological activities of 2,4-diamino-5-chloro-6-substituted quinazolines]. 182 76

Sequential methotrexate (Mtx) absorption studies were undertaken in 127 children undergoing treatment for childhood non-T acute lymphoblastic leukaemia (ALL) to determine whether serum drug concentration, clearance and dosage affect event free survival (EFS). Higher serum concentration and area under the plasma concentration curve (AUC) were not associated with an improved EFS. Methotrexate clearance was not found to be of prognostic significance. Patients who tolerated only low 6-mercaptopurine (6-MP) doses because of neutropaenia and those who randomly were prescribed higher doses of Mtx had a lower rate of leukaemia relapse after the completion of therapy. This suggests that the use of maintenance therapy in maximally tolerated doses may be associated with an increased survival in childhood ALL.
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PMID:The influence of serum methotrexate concentrations and drug dosage on outcome in childhood acute lymphoblastic leukaemia. 163 72

The elderly patients with lymphoma suffer from a relevant excess mortality, both during treatment and in the course of follow-up: various causes contribute, including: 1) "generational" mortality; 2) iatrogenic mortality due to unexpected organ/system fragility; 3) low remission rates, due to low tolerated doses and, 4) a high prevalence of second tumors. The difficulty in achieving high cure rates begins after age 50 and steadily increases for patients over 60, 70 and 80. Less aggressive staging procedures are justified, and the modern visualizing techniques provide alternatives to lymphangiography and laparosplenectomy. In HD, local radiation instead of Total Nodal Irradiation, and doses of 30 or even 20 Gy may be administered for stages I and II; for stages III and IV the ChlVPP and the NOVP or the "ABVD without D" regimens may be adopted. After chronological and/or biological age 80, sequentially administered single agents produce an effective palliation, allowing for a good quality of life during treatment, and often obtain a reasonable prolongation of survival. Many NHL of elderly patients are indolent in their course, and a "watch and wait" policy is often in the true interest of the patient; when local aggressiveness only is apparent, a local low dose radiation may be considered. For advanced stage, treatment-requiring low-grade-NHL, oral chlorambucil plus or minus low dose steroids (or prednimustine) should be considered in alternative to watch and wait. For high grade, aggressive NHL, chemotherapy with short, non-Methotrexate-containing programs like POCE, NOSTE, P-VABEC, or other variations of MACOP-B are acceptable. Beyond age 80, or when other factors deteriorate the chances for survival, single agents like VM 26, or simple combinations of VP 16 + Prednimustine or VP 16 and Mitoxantrone may be adopted.
Leukemia 1991
PMID:Lymphomas in the elderly. 189 Aug 72

HO-221, N-[4-(5-bromo-2-pyrimidinyloxy)-3-chlorophenyl]-N'-(2- nitrobenzoyl) urea is a new benzoylphenylurea derivative. The compound exhibits significant antitumor effects against various animal tumors, and was especially effective against the solid tumors implanted subcutaneously. HO-221 inhibits DNA polymerase alpha activity strongly in vitro. In this study, we examined the cross-resistance of HO-221 to various antitumor agents using sublines of mouse leukemia. HO-221 showed antitumor effects in mice bearing L 1210 or P 388 leukemia resistant to 10 antitumor agents, DM (daunomycin), MMC (mitomycin C), CDDP (cisplatin), 5-FU (5-fluorouracil), Ara-C (cytosine arabinoside), MTX (methotrexate), CPA (cyclophosphamide), CQ (carboquone), ADM (adriamycin) and VCR (vincristine), respectively. These antitumor agents were also effective in P 388 leukemia resistant to HO-221 (P 388/HO-221). Furthermore, CDDP- and MMC-resistant sublines showed a collateral sensitivity to HO-221 in vivo. The grow the inhibitory effects were also noted in vitro in ADM-, CDDP- and MMC-resistant cells by HO-221. However, the in vitro experiments didn't show such collateral sensitivity on the resistant sublines. These results suggest that there is no cross-resistance between HO-221 and other known antitumor agents, and that HO-221 seemed to be worth for evaluating clinical usefulness.
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PMID:[Cross-resistance of HO-221 and various antitumor agents in sublines of mouse leukemia]. 189 47

We prospectively compared neuropsychologic functioning and clinical indicators of neurotoxicity in 49 consecutive childhood leukemia patients in long-term continuous complete remission (CR) who had received two different regimens of CNS prophylaxis by random assignment. Twenty-three patients were treated with 1,800 cGy cranial radiation and intrathecal methotrexate (RT group) and 26 with parenteral methotrexate only (MTX group). Over half of the RT group had somnolence syndrome, and four developed cerebral calcifications late in their clinical course. Abnormal electroencephalograms (EEGs) were seen in 15 patients in the MTX group, and six had early, transient white-matter hypodensities apparent on computed tomographic (CT) scans. Mean scores on standard tests of intelligence and academic achievement, administered after remission induction and again at a median of 6 years after treatment cessation, did not differ significantly between the two groups. However, statistically significant decreases in overall and verbal intelligence quotients (IQs) and in arithmetic achievement were found within both treatment groups. Sixteen of 26 in the MTX group and 14 of the 23 in the RT group had clinically important decreases (greater than or equal to 15 points) on one or more neuropsychologic measures. These changes did not correlate with findings on CT scans, EEGs, or other clinical signs of neurotoxicity. We conclude that 1,800 cGy cranial radiation and parenteral methotrexate, as used in this study, are associated with comparable decreases in neuropsychologic function.
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PMID:Comparison of neuropsychologic functioning and clinical indicators of neurotoxicity in long-term survivors of childhood leukemia given cranial radiation or parenteral methotrexate: a prospective study. 198 64

Plasma homocysteine was determined in 12 children with acute lymphoblastic leukemia. The patients were investigated prior to chemotherapy (stage I), during seven weeks of induction chemotherapy (stage II), and thereafter during intermittent high-dose methotrexate (HD-MTX) therapy (stage III). The patients were followed for a period of three to 15 months, and the study included a total of 80 HD-MTX courses. Before start of chemotherapy (stage I), the average plasma homocysteine level in the children with leukemia was 13.18 +/- 6.23 (SD) mumol/liter, which is significantly (P less than 0.001) higher than the level in control children (6.52 +/- 1.21 mumol/liter). The plasma homocysteine level in the patients was positively correlated with the peripheral white blood cell count (P less than 0.01) and negatively correlated with serum folate (P less than 0.02). The serum folate was normal or subnormal in these patients. During induction therapy with cytotoxic drugs such as vincristine, asparaginase, and intrathecal MTX (stage II), there was a drastic change in plasma homocysteine as a function of time. A reciprocal alteration in serum folate was observed, suggesting fluctuating intracellular folate status at this stage of therapy. At the end of stage II (about seven weeks), there was a significant (P less than 0.01) reduction in total homocysteine (to 7.08 +/- 3.84 mumol/liter). HD-MTX (8 g/m2) therapy with 5-formyltetrahydrofolate "rescue" (stage III) was usually begun about seven weeks after start of chemotherapy, and the patients were followed for two to eight courses separated by three to eight weeks. Plasma homocysteine showed a transient increase (26-64%) following each MTX infusion. After three MTX infusions, basal total plasma homocysteine was reduced to 5.56 +/- 1.12 mumol/liter. During most MTX infusions, there was a variable reduction (17-56%) in plasma methionine followed by a rebound increase. It is concluded that plasma homocysteine in children with acute lymphoblastic leukemia is elevated prior to therapy, probably because of occasional folate deficiency and increased burden of proliferating cells. During induction therapy, monitoring plasma homocysteine and serum folate both suggest a labile folate homeostasis, usually a deficiency state. HD-MTX induced a temporary intracellular folate depletion before 5-formyl-tetrahydrofolate was administered, as judged by a transient homocysteinemia. The methionine depletion may interfere with the antileukemic effect of MTX.
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PMID:Plasma homocysteine in children with acute lymphoblastic leukemia: changes during a chemotherapeutic regimen including methotrexate. 198 22

Photopenic areas on bone scintigraphy is a rare presentation of childhood leukemia. This includes the more common acute lymphocytic leukemia as well as the far less common myelomonocytic leukemia. Other causes of photopenia on bone scintigraphy in these patients include relapse with marrow replacement and associated bone necrosis. Methotrexate therapy has also previously been described as showing similar photopenic areas secondary to bone necrosis.
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PMID:Photopenic areas on bone scanning associated with childhood leukemia. 199 51


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